Low-level lead exposure promotes hepatic gluconeogenesis and contributes to the elevation of fasting glucose level

Wan, Heng; Wang, Bin; Cui, Yuke; Wang, Yuying; Zhang, Kun; Chen, Chi; Xia, Fangzhen; Ye, Lin; Wang, Li; Wang, Ningjian; Lu, Yingli

doi:10.1016/j.chemosphere.2021.130111

Cited by 25 publications

(15 citation statements)

References 39 publications

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“…Several reports have documented the relationship between Pb exposure and glucose dys‐metabolism, as well as complications related to diabetes 7,30,31 . However, we observed that exposures to Pb and MPs alone had no statistically significant difference on insulin resistance, although the Pb exposure showed a tendency to increase insulin resistance.…”

Section: Discussioncontrasting

confidence: 54%

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Combined exposure to lead and microplastics increased risk of glucose metabolism in mice via the Nrf2/NF‐κB pathway

Zhu,

Li,

et al. 2024

Environmental Toxicology

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The purpose of this study was to explore the effects of combined lead (Pb) and two types of microplastic (MP) (polyvinyl chloride [PVC] and polyethylene [PE]) exposure on glucose metabolism and investigate the role of the nuclear factor erythroid 2‐related factor 2 (Nrf2)/nuclear factor‐kappa B (NF‐κB) signaling pathway in mediating these effects in mice. Adult C57BL/6J mice were randomly divided into four groups: control, Pb (100 mg/L), MPs (containing 10 mg/L PE and PVC), and Pb + MPs, each of which was treated with drinking water. Treatments were conducted for 6 weeks. Co‐exposure to Pb + MPs exhibited increase glycosylated serum protein levels, insulin resistance, and damaged glucose tolerance compared with the control mice. Additionally, treatment with Pb + MPs caused more severe damage to hepatocytes than when exposed to them alone concomitantly, exposed to Pb + MPs exhibited improved the levels of interleukin‐6, tumor necrosis factor‐alpha, and malondialdehyde, but reduced superoxide dismutase, glutathione peroxidase, and catalase assay in livers. Furthermore, they increase the Kelch‐like ECH‐associated protein 1 (Keap1) and phosphorylated p‐NF‐κB protein levels but reduced the protein levels of heme oxygenase‐1 and Nrf2, as well as increased Keap1 mRNA and Nrf2 mRNA. Co‐exposure to Pb + MP impacts glucose metabolism via the Nrf2 /NF‐κB pathway.

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Section: Discussioncontrasting

confidence: 54%

“…Although Pb is an endocrine disrupting chemical, few studies have investigated the impact of low‐dose Pb exposure on the levels of blood glucose. Recently, emerging evidence indicated that Pb exposure may induce the increased production of hepatic glucose and eventually develop into type 2 diabetes mellitus (T2DM) 7 …”

Section: Introductionmentioning

confidence: 99%

Combined exposure to lead and microplastics increased risk of glucose metabolism in mice via the Nrf2/NF‐κB pathway

Zhu,

Li,

et al. 2024

Environmental Toxicology

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“…In addition to Cu and Ga, other metals, including Mn, Fe, Ni, Rb, Sr, Pb, Co, and V, also exhibited significant associations with GDM in the single-exposure analysis, although they exhibited a much lower relative importance in the mixture effect. Epidemiological studies have reported the associations of single exposure to these metals with GDM or T2D. ,,,− Toxicological investigations also reported that selected metals (e.g., Mn, Ni, Pb, and Co) could disrupt glucose uptake and alter related molecular mechanisms involved in glucose metabolism and homeostasis regulations. − Therefore, gestational exposure to such a complexity of metals collectively elevated the GDM risk.…”

Section: Discussionmentioning

confidence: 99%

Metal Exposure during Early Pregnancy and Risk of Gestational Diabetes Mellitus: Mixture Effect and Mediation by Phospholipid Fatty Acids

Sun,

Pan,

et al. 2023

Environ. Sci. Technol.

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Despite existing studies exploring the association between metal exposure and gestational diabetes mellitus (GDM), most of them have focused on a single metal or a small mixture of metals. Our prospective work investigated the joint and independent effects of early gestational exposure to 17 essential and nonessential metals on the GDM risk and potential mediation by plasma phospholipid fatty acids (PLFAs) based on a nested case−control study established with 335 GDM cases and 670 randomly matched healthy controls. The Bayesian kernel machine regression (BKMR) and quantile g-computation analyses demonstrated a joint effect from metal co-exposure on GDM risk. BKMR with hierarchical variable selection indicated that the group of essential metals was more strongly associated with GDM than the group of nonessential metals with group posterior inclusion probabilities (PIPs) of 0.979 and 0.672, respectively. Cu (0.988) and Ga (0.570) had the largest conditional PIPs within each group. We also observed significant mediation effects of selected unsaturated PLFAs on Cu−GDM and Ga−GDM associations. KEGG enrichment analysis further revealed significant enrichment in the biosynthesis of unsaturated PLFAs. C18:1 n-7 exhibited the largest proportion of mediation in both associations (23.8 and 22.9%). Collectively, our work demonstrated the joint effect of early gestational metal exposure on GDM risk and identified Cu and Ga as the key species to the joint effect. The findings lay a solid ground for further validation through multicenter investigations and mechanism exploration via laboratory studies.

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“…Lead exposure at any level is unsafe. A previous study confirmed that lead can negatively affect human health even at low levels because long-term exposure to lead has a cumulative effect [ 11 ], and affects organs differently, being associated with heart failure [ 12 ], inhibition of hepatic gluconeogenesis [ 13 ], ovarian damage [ 14 ], and nephrotoxicity [ 15 ]. Moreover, it can spread between organs and tissues, causing accumulation in the intestines, lungs, liver, spleen, kidneys, central nervous system and bones, thereby interfering with a variety of physiological processes [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Patterns of global burden of 13 diseases attributable to lead exposure, 1990–2019

Lin

Cao

et al. 2023

BMC Public Health

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Objectives Understanding the spatio-temporal patterns of the global burden of various diseases resulting from lead exposure is critical for controlling lead pollution and disease prevention. Methods Based on the 2019 Global Burden of Disease (GBD) framework and methodology, the global, regional, and national burden of 13 level-three diseases attributable to lead exposure were analyzed by disease type, patient age and sex, and year of occurrence. Population attributable fraction (PAF), deaths and disability-adjusted life years (DALYs), age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) obtained from the GBD 2019 database were used as descriptive indicators, and the average annual percentage change (AAPC) was estimated by a log-linear regression model to reflect the time trend. Results and conclusions From 1990 to 2019, the number of deaths and DALYs resulting from lead exposure increased by 70.19% and 35.26%, respectively; however, the ASMR and ASDR decreased by 20.66% and 29.23%, respectively. Ischemic heart disease (IHD), stroke, and hypertensive heart disease (HHD) showed the highest increases in deaths; IHD, stroke, and diabetes and kidney disease (DKD) had the fastest-growing DALYs. The fastest decline in ASMR and ASDR was seen in stroke, with AAPCs of -1.25 (95% CI [95% confidence interval]: -1.36, -1.14) and -1.66 (95% CI: -1.76, -1.57), respectively. High PAFs occurred mainly in South Asia, East Asia, the Middle East, and North Africa. Age-specific PAFs of DKD resulting from lead exposure were positively correlated with age, whereas the opposite was true for mental disorders (MD), with the burden of lead-induced MD concentrated in children aged 0–6 years. The AAPCs of ASMR and ASDR showed a strong negative correlation with the socio-demographic index. Our findings showed that the global impact of lead exposure and its burden increased from 1990 to 2019 and varied significantly according to age, sex, region, and resulting disease. Effective public health measures and policies should be adopted to prevent and control lead exposure.

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Low-level lead exposure promotes hepatic gluconeogenesis and contributes to the elevation of fasting glucose level

Cited by 25 publications

References 39 publications

Combined exposure to lead and microplastics increased risk of glucose metabolism in mice via the Nrf2/NF‐κB pathway

Combined exposure to lead and microplastics increased risk of glucose metabolism in mice via the Nrf2/NF‐κB pathway

Metal Exposure during Early Pregnancy and Risk of Gestational Diabetes Mellitus: Mixture Effect and Mediation by Phospholipid Fatty Acids

Patterns of global burden of 13 diseases attributable to lead exposure, 1990–2019

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